• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.311-317
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• 2001

YHB6211, a newly developed recombinant human granulocyte colonystimulating factor, was administered at dose levels of 0, 3, 15, and 75 $\mu$g/kg/day intravenously to the pregnant New Zealand White rabbits (20 rabbits per group) during the organogenetic period, days 6 to 18 of gestation. All dams were subjected to Caesarian section on day 28 of gestation and their fetuses were examined for external, visceral, and skeletal abnormalities. No abnormalities in clinical signs, body weight changes, gross findings, mortality, and external appearance were found in all dams and fetuses exposed to 0, 3, and 15 $\mu$g/kg/day of YHB6211. However, in the group treated with 75 $\mu\textrm{g}$/kg/day of YHB6211, maternal body and uterine weights, fetal body weights and length, and the number of live fetuses were significantly decreased and further fetal mortality was remarkably increased. It is suggested that YHB6211 may have no side effect up to the dose level of 15 $\mu$g/kg/day, and there would be no teratogenicity for fetuses of rabbits up to 75 $\mu\textrm{g}$/kg/day even if it may have some toxic effects over 75$\mu\textrm{g}$/kg/day for dams and fetuses of rabbits.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2005.10a
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• pp.130-130
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• 2005

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2005.10a
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• pp.130-130
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• 2005

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.310-315
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• 1994

The pharmacokinetics and tissue distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor, rhG-CSF, recently manufactured by Dong-A research laboratory of Dong-A Pharmaceutical Company) were compared with reported data in the literature. After intravenous(i.v.) administration of DA-3030, at dose of 5, 10 and 100 $\mu\textrm{g}$/kg to rats, some pharmacokinetic parameters, such as terminal half-lives(1.05, 1.19 and 1.83 hr, respectively) and clearance (84.0, 54.8 and 45.5 mι/hr/kg, repectively), were dose-dependent. This could be due to the saturable metabolism of DA-3030 in rats. Similar results were also reported. After subcutaneous(s.c.) and intramuscular(i.m.) administrations of DA-3030, 10 $\mu\textrm{g}$/kg to rats, the extent of bioavailability(absolute bioavailability) were incomplete; the values were 23.3 and 18.2% after s.c. and i.m. injections, respectively, due to the degradation of DA-3030 by protease. After 7-consecutive day i.v. administrations of DA-3030, 10 $\mu\textrm{g}$/kg/day, to rats, the plasma concentrations and pharmacokinetic parameters of DA-3030 were not significantly different from those in single administration. In mice and dogs at DA-3030 dose of 10 $\mu\textrm{g}$/kg, the plasma concentrations of DA-3030 were also declined rapidly with terminal half-lives of 1.31 and 1.15 hr, respectively. DA-3030 was highly concentrated in the kidney after i.v. administration of DA-3030, 10 $\mu\textrm{g}$/kg, to rats, and the results were similar to those obtained using radiolabelled rhG-CSF in the literature. Above data indicate that DA-3030 has similar properties to rhG-CSF manufactured by other companies in view of pharmacokinetics.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.145-150
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• 1998

Administration of 3 type KGCs [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose dependent increase in the peripheral blood neutrophil count 6 hours after the final KGC injection. Within the KGC dose range of 0.1 to 40$\mu$g Per mouse Per day, there was a sigmoidal relationship between the logarithm of the dose and the peripheral blood neutrophil count (relative value for neutrophil count of the basal dose) in the treated mice. The sigmoidal relationship of test KGC preparations shows that there is a saturation point in terms of efficacy. Compared with e(fact of KGC-Orange, Green, and Blue, KGC-Orange recovers neutrophils more effectively than the others do.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.447-448
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• 2001

Human garnulocyte-colony stimulating factor(hG-CSF), a hematopoietic growth factor$^{1)}$, was produced and secreted from tobacco cell suspension. hG-CSF produced from tobacco cell suspension culture is biologically active form. The produced amount of hG-CSF is about 100${\mu}g/L$ in 9 days after inoculation.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.165.3-166
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• 2001

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.213-216
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• 2000

In vivo administration of Leucostim, a human recombinant granulocyte colony-stimulating factor (G-CSF), was evaluated for the effects on survival, hematologic recovery, and colony forming unit- spleen (CFU-5) in murine bone marrow transplantation (BMT) model. Sublethally irradiated (9 Gy) mice received bone marrow cells from untreated mice, and then were treated with G-CSF subcutaneously at doses of 2.5,5, or $10\mu\textrm{g}$/kg or vehicle solution (control) for 14 days from one day after BMT. There was no effect of irradiation and BMT on mortality. The repeated subcutaneous injections of Leucostim for 14 days post- BMT significantly facilitated hematologic recovery compared with vehicle control in a dose-dependent manner. Moreover, mice treated with Leucostim had significantly increased numbers of CFU-s colonies on day 10 post-BMT. These results suggest that Leucostim, a new G-CSF, has beneficial effects on hematologic reconstitution after BMT.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.281-285
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• 1994

Neutropenia is a major dose-limiting factor in cancer chemotherapy diminishing its usefulness and increase patient's susceptibility to infectious disease. Some recombinant human granulocyte colony stimulating factors(rhG-CSFs) are in use to reduce the risk of this serious side effect. In this study, we examined the pharmacological properties of DA-3030, a rhG-CSF expressed in E. coli. DA-3030 100 and $\mu\textrm{g}$/kg, i. v., had no significant effect on the central nervous, gastrointestinal system in mice and cardiovascular system in rabbits, but it slightly inhibited the spontaneous motility of isolated nonpregnant uterus in rats. It also had no influence on excretion of urinary electrolytes. DA-3030 administered for successive 3 days increased the blood WBC count in zymosan air pouch inflammed rats and in normal rats. These results indicate that DA-3030 has little side effects in animals.